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<article article-type="research-article" dtd-version="1.1" specific-use="sps-1.9" xml:lang="en" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">
	<front>
		<journal-meta>
			<journal-id journal-id-type="publisher-id">dic</journal-id>
			<journal-title-group>
				<journal-title>ABC Imagem Cardiovascular</journal-title>
				<abbrev-journal-title abbrev-type="publisher">Arq Bras Cardiol: Imagem cardiovasc.</abbrev-journal-title>
			</journal-title-group>
			<issn pub-type="epub">2675-312X</issn>
			<publisher>
				<publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
			</publisher>
		</journal-meta>
		<article-meta>
			<article-id pub-id-type="doi">10.36660/abcimg.20230027i</article-id>
			<article-categories>
				<subj-group subj-group-type="heading">
					<subject>Original Article</subject>
				</subj-group>
			</article-categories>
			<title-group>
				<article-title>Pulmonary Congestion in Heart Failure With Reduced Ejection Fraction: Comparison Between Lung Ultrasound and Remote Dielectric Sensing</article-title>
			</title-group>
			<contrib-group>
				<contrib contrib-type="author">
					<contrib-id contrib-id-type="orcid">0000-0002-2634-4632</contrib-id>
					<name>
						<surname>Otto</surname>
						<given-names>Maria Estefânia Bosco</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>acquisition of data</role>
					<role>analysis and interpretation of the data and critical revision of the manuscript for intellectual content</role>
					<role>statistical analysis</role>
					<role>writing of the manuscript</role>
					<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Esmanhoto</surname>
						<given-names>Vanessa Andreoli</given-names>
					</name>
					<role>acquisition of data</role>
					<role>analysis and interpretation of the data and critical revision of the manuscript for intellectual content</role>
					<role>writing of the manuscript</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Correia</surname>
						<given-names>Edileide de Barros</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Murta</surname>
						<given-names>Ana Cristina de Souza</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Bruscky</surname>
						<given-names>Larissa Ventura Ribeiro</given-names>
					</name>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Vilela</surname>
						<given-names>Andrea de Andrade</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>acquisition of data</role>
					<role>analysis and interpretation of the data and critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Paladino</surname>
						<given-names>Antonio Tito</given-names>
						<suffix>Filho</suffix>
					</name>
					<role>Conception and design of the research</role>
					<role>acquisition of data</role>
					<role>analysis and interpretation of the data and critical revision of the manuscript for intellectual content</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Assef</surname>
						<given-names>Jorge Eduardo</given-names>
					</name>
					<role>Conception and design of the research</role>
					<role>analysis and interpretation of the data and critical revision of the manuscript for intellectual content</role>
					<role>writing of the manuscript</role>
					<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1">
				<label>1</label>
				<institution content-type="orgname">Instituto Dante Pazzanese de Cardiologia</institution>
				<addr-line>
					<named-content content-type="city">São Paulo</named-content>
					<named-content content-type="state">SP</named-content>
				</addr-line>
				<country country="BR">Brazil</country>
				<institution content-type="original">Instituto Dante Pazzanese de Cardiologia, São Paulo, SP – Brazil</institution>
			</aff>
			<aff id="aff2">
				<label>2</label>
				<institution content-type="orgname">Instituto de Cardiologia e Transplante do Distrito Federal</institution>
				<addr-line>
					<named-content content-type="city">Brasília</named-content>
					<named-content content-type="state">DF</named-content>
				</addr-line>
				<country country="BR">Brazil</country>
				<institution content-type="original">Instituto de Cardiologia e Transplante do Distrito Federal, Brasília, DF – Brazil</institution>
			</aff>
			<author-notes>
				<corresp id="c01"> Mailing Address: Maria Estefânia Bosco Otto • Instituto de Cardiologia do Distrito Federal (ICDF): Ecocardiograma. SQSW 301. Bloco F. Ap 508. Postal Code: 70673-106. Brasília, DF – Brazil E-mail: <email>mariaestefaniaotto@gmail.com</email>
				</corresp>
				<fn fn-type="conflict">
					<p>Potential Conflict of Interest</p>
					<p>No potential conflict of interest relevant to this article was reported.</p>
				</fn>
				<fn fn-type="edited-by">
					<p>Editor responsável pela revisão: Daniela do Carmo Rassi Frota</p>
				</fn>
			</author-notes>
			<pub-date date-type="pub" publication-format="electronic">
				<day>24</day>
				<month>05</month>
				<year>2023</year>
			</pub-date>
			<pub-date date-type="collection" publication-format="electronic">
				<month>05</month>
				<year>2023</year>
			</pub-date>
			<volume>36</volume>
			<issue>2</issue>
			<elocation-id>e20230027</elocation-id>
			<history>
				<date date-type="received">
					<day>10</day>
					<month>03</month>
					<year>2023</year>
				</date>
				<date date-type="rev-recd">
					<day>16</day>
					<month>03</month>
					<year>2023</year>
				</date>
				<date date-type="accepted">
					<day>16</day>
					<month>03</month>
					<year>2023</year>
				</date>
			</history>
			<permissions>
				<license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
					<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
				</license>
			</permissions>
			<abstract>
				<title>Abstract</title>
				<sec>
					<title>Backgound</title>
					<p> Outpatient assessment of pulmonary congestion in patients with heart failure with reduced ejection fraction (HFREF) can minimize hospitalizations due to decompensation and optimize the use of diuretics.</p>
				</sec>
				<sec>
					<title>Objective</title>
					<p> To compare the remote dielectric sensor (REDS), a validated device for detecting pulmonary extravascular fluid, with clinical parameters, transthoracic echocardiogram (TTE) and lung ultrasound (ULSP).</p>
				</sec>
				<sec>
					<title>Methods</title>
					<p> We included 38 patients from heart failure clinic (63±12 years; 21 men). All were submitted within 24 hours to clinical evaluation with description of paroxysmal nocturnal dyspnea, leg edema (LE), presence of dizziness; laboratory evaluation of NT-ProBNP; evaluation by REDS and TTE with analysis of parameters of systemic congestion by the inferior vena cava evaluation, function of the right ventricle and of pulmonary congestion, such as evaluation of filling pressures by average of E/e’ and indexed left atrial volume. The ULSP was performed using the 8 points anterior quadrants protocol, counting B lines in one respiratory cycle.</p>
				</sec>
				<sec>
					<title>Results</title>
					<p> 22 patients had REDS ≥ 35% (indicative of pulmonary congestion) and 16 patients REDS&lt;35%. Clinical and echocardiographic parameters were compared with REDS ≥ 35%. In the multivariate analysis, the variables body surface area, B lines and LE were associated with REDS ≥ 35%. NT-ProBNP was similar and elevated in both groups.</p>
				</sec>
				<sec>
					<title>Conclusions</title>
					<p> Outpatient monitoring of HFREF for volume control can be sensitized by the presence of B lines on the ULSP with good correlation to REDS ≥ 35%. NT pro BNP was not able to differentiate patients with congestion detected by REDS.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="en">
				<kwd>Ultrasonography</kwd>
				<kwd>Lung</kwd>
				<kwd>Heart Failure</kwd>
			</kwd-group>
			<counts>
				<fig-count count="4"/>
				<table-count count="8"/>
				<equation-count count="0"/>
				<ref-count count="24"/>
			</counts>
		</article-meta>
	</front>
	<body>
		<sec sec-type="intro">
			<title>Introduction</title>
			<p>Outpatient evaluation of the blood volume status of patients with heart failure with reduced ejection fraction (HFrEF), regardless of etiology, is complex and requires the integration of clinical and laboratory signs.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> Early detection of higher blood volume by invasive methods was able to improve the optimization of pharmacological treatment, as well as avoid hospitalizations and complications, such as renal failure and inappropriate increase of diuretics.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> However, the outpatient management of patients with HFrEF cannot use invasive methods, needing the analysis of clinical parameters associated with imaging methods, such as echocardiography<sup><xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr" rid="B6">6</xref></sup> and lung ultrasound (LUS).<sup><xref ref-type="bibr" rid="B7">7</xref>-<xref ref-type="bibr" rid="B9">9</xref></sup></p>
			<p>Recently, a new volume assessment technology,<sup><xref ref-type="bibr" rid="B10">10</xref></sup> called ReDS (Remote Dielectric Sensing: Sensible Medical Innovations, Ltd, Klar Neter, Israel), has shown promising results in monitoring extravascular lung fluid, including validation by tomography.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> Nevertheless, LUS has not been compared with ReDS performed in outpatient clinics to monitor patients with HFrEF and difficult therapeutic management. The advantage of using LUS associated with physical examination and laboratory analysis is its low cost, easy training, and good reproducibility.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup></p>
			<p>Thus, this study aimed to compare LUS with ReDS as the gold standard for extravascular lung fluid analysis in the diagnosis of pulmonary congestion among outpatients with HFrEF and difficult therapeutic management. Moreover, clinical, echocardiographic, and laboratory parameters were added to this analysis to provide sensitivity to the detection of systemic blood volume balance in this patient group.</p>
		</sec>
		<sec sec-type="methods">
			<title>Methods</title>
			<p>In this prospective cohort pilot study, conducted from December 2021 to February 2022, we included patients over 18 years selected from the cardiomyopathy outpatient clinic of the Instituto Dante Pazzanese de Cardiologia (IDPC) who receive serial follow-up at the volume outpatient clinic because they have HFrEF with difficult volume control. Informed consent was obtained from each patient, and the study protocol complies with the ethical guidelines of the 1975 Helsinki Declaration. The IDPC Research Committee approved the protocol under the Certificate of Presentation for Ethical Consideration number 53224821.0.0000.5462.</p>
			<sec>
				<title>Cases and study design</title>
				<p>Patients with HFrEF and difficult volume control are evaluated in a specific IDPC outpatient clinic to reduce complications that may occur by the use of high doses of diuretics and earlier returns. In this scenario, the inclusion of patients could be concentrated on these days so that ReDS could be available for IDPC once a week, with echocardiography — focused on the analysis of parameters related to volume — and LUS — for the evaluation of B-lines — performed on the same day or in the next morning. The researchers responsible for ultrasound evaluations were not aware of the volume result obtained by ReDS.</p>
				<p>We included 38 consecutive patients with HFrEF of various etiologies. Inclusion was based on the availability of ReDS and the possibility of timely performing the echocardiography and LUS.</p>
			</sec>
			<sec>
				<title>Clinical evaluation</title>
				<p>The selected patients were evaluated in routine outpatient visits. The following clinical data were chosen for comparison with the volume state: weight, body surface area (BSA), body mass index (BMI), lower extremity edema (LEE), and functional class by <italic>the New York Heart Association.</italic><sup><xref ref-type="bibr" rid="B1">1</xref></sup> An experienced clinical cardiologist supervised and checked all clinical examinations.</p>
			</sec>
			<sec>
				<title>Laboratory evaluation</title>
				<p>Following the clinical evaluation, NT-proBNP was collected. The collection and analysis of blood tests were performed by IDPC’s clinical laboratory. Collection standardization, methods, and analysis equipment are in accordance with the service routine.</p>
			</sec>
			<sec>
				<title>Use of ReDS</title>
				<p>After the collection of laboratory tests, the volunteers underwent a ReDS (Sensible Medical Innovations, Ltd, Klar Neter, Israel) evaluation. The ReDS technology consists of a miniature radar that transmits low-power electromagnetic signals to the body.<sup><xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup> It can be used to evaluate the patient with a chest vest (<xref ref-type="fig" rid="f01">Figure 1</xref>). Two sensors integrated into the vest are attached to the body: one in the anterior chest, on the right side, and the other in the posterior back. Each sensor can transmit and receive the beam of electromagnetic waves passing through the lung. The reflected signal is analyzed, translating the dielectric properties of the lung tissue between the sensors. Because water has a very high dielectric coefficient, tissue dielectric coefficients are predominantly determined by their fluid content.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> A healthy human lung (for an average person with 70 kg) has 450 to 500 mL of blood. The extravascular compartment usually has another 250 to 700 mL of fluid. As the normal total lung air volume is 1.8 to 2.2 L, considering a tidal volume of 500 mL, the normal intrathoracic fluid content can be estimated to vary between 20 and 34% of the total volume.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> This range was confirmed by density measurements performed by different quantitative imaging technologies.<sup><xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup></p>
				<p>
					<fig id="f01">
						<label>Figure 1</label>
						<caption>
							<title>– ReDS. Image provided by the ReDS manufacturer (Remote Dielectric Sensing: Sensible Medical Innovations, Ltd, Klar Neter, Israel).</title>
						</caption>
						<graphic xlink:href="2675-312X-dic-36-02-e20230027-gf01.tif"/>
					</fig>
				</p>
				<p>ReDS measurements were taken by professionals trained to use the device. These patients remained seated at rest with the ReDS for 45 seconds, after which the device automatically provided the percentage of thoracic fluid. The normal value is defined as up to 34%, possible hypervolemia as 35–50%, significant hypervolemia as above 50%, and hypovolemia as below 20% (manufacturer data).</p>
			</sec>
			<sec>
				<title>LUS</title>
				<p>LUS was performed on GE Vivid E95 equipment (GE Health Care, Norway), using the eight-point anterior segment protocol with a 2-5 MHz sector transducer and the echocardiography device adjusted for “abdominal” mode. Images were acquired in 6 seconds, allowing the evaluation of a respiratory cycle. This protocol is called BLUE (Bedside Lung Ultrasound in Emergency),<sup><xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B17">17</xref>-<xref ref-type="bibr" rid="B19">19</xref></sup> with the patient at a 45-degree chest inclination in the bed. The protocol aims to evaluate the presence of B-lines — artifacts formed in the LUS due to the increase in parenchymal fluid — and count them in each segment during a respiratory cycle (<xref ref-type="fig" rid="f02">Figure 2</xref>).<sup><xref ref-type="bibr" rid="B19">19</xref></sup> The finding of more than three B-lines in 2 quadrants of each hemithorax means congestion in patients with HFrEF. We chose to count the total of B-lines in both hemithorax.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B19">19</xref></sup> This evaluation was performed by a trained examiner, who had no knowledge of the patient’s clinical condition or of the results of laboratory tests and the estimated blood volume in the ReDS. Images were recorded and saved on specific media so that another professional involved in the study could analyze the B-line count variability.</p>
				<p>
					<fig id="f02">
						<label>Figure 2</label>
						<caption>
							<title>– Schematic representation of the Bedside LUS in Emergency (BLUE) protocol. A) Analysis of the anterior thorax; B) Analysis of the lateral area using the posterior axillary line as a reference.</title>
						</caption>
						<graphic xlink:href="2675-312X-dic-36-02-e20230027-gf02.tif"/>
						<attrib>Location model of points to be assessed in LUS using the BLUE protocol. A) Both hands are placed in the patient’s hemithorax with the upper little finger right below the clavicle (black line above the little finger); excluding the thumbs, the lower part of the other hand is placed at the level of the diaphragm line (black line). The point called “upper BLUE” (red dot) is in the middle of the upper hand. The “lower BLUE point” is in the middle of the lower palm. These four points roughly follow the lung anatomy and avoid the heart area. B) The point of the costophrenic recess area (red dot) is built from the horizontal line continuing from the lower BLUE point and the vertical line continuing the posterior axillary line (black line). Lastly, an upper point can be added between the posterior and anterior axillary lines in the upper thorax. That way, we would have 4 points in each hemithorax. Image created by Maria Estefânia Bosco Otto, MD.<sup>19</sup></attrib>
					</fig>
				</p>
			</sec>
			<sec>
				<title>Echocardiography</title>
				<p>The echocardiography with assessment measurements for the biventricular function and specific parameters related to blood volume was performed concomitantly with LUS, on the same equipment, and by the same professional, who only changed the image analysis mode to “adult echocardiography”. We evaluated the following left ventricle (LV) parameters: systolic diameter, diastolic diameter, and ejection fraction (EF) by Simpson’s biplane method; LV outflow tract velocity time integral (LVOT VTI); integrated measures of diastolic function, such as mitral E-wave velocity, mitral A-wave velocity, E/A ratio, tissue Doppler of the septal and lateral mitral annulus to evaluate the e’ wave velocity, mean E/e’ ratio, left atrial volume (LAV), and pulmonary artery systolic pressure by continuous Doppler of tricuspid regurgitation; semi-quantitative assessment of right ventricular function with tricuspid annular plane systolic excursion (TAPSE) analysis, tricuspid lateral annular systolic velocity, and subjective evaluation; right atrial pressure (RAP) assessment with analysis of the inferior vena cava (IVC) according to guidelines of the American Society of Echocardiography.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup></p>
				<p>Echocardiographic images were recorded and saved in specific media.</p>
			</sec>
			<sec>
				<title>Statistical analysis</title>
				<p>We compared imaging and clinical parameters among patients with ReDS &lt;35% and ≥35% using Student’s <italic>t</italic> test or the non-parametric Mann-Whitney test for quantitative variables and the chi-square test or exact chi-square test for qualitative variables.</p>
				<p>Evaluation of independent indicators of pulmonary congestion consisted of comparing heart and clinical parameters and adjustment of Poisson regression models with robust variance for the ReDS ≥35% result associated with epidemiological, vital signs, and anthropometric variables, LV mass, volume, and function, diastolic function, right ventricle (RV), IVC, and clinical variables, adopting prevalence ratio and their respective confidence intervals as the effect measure. The analysis had two stages: univariate and multivariate. In both, we calculated prevalence ratios and their respective 95% confidence intervals.</p>
				<p>The univariate analysis revealed an association between each independent variable and ReDS≥35%; those with p&lt;0.25 were included in the multivariate analysis. In the multivariate analysis, the models were constructed by the consecutive exclusion of a variable with the highest p-value in the Wald test from each complete model, as described by Hosmer and Lemeshow, followed by the readjustment and verification of the model stability after the removal of each variable, in order to obtain a more parsimonious model, with a better fit to the data. Once the final model was obtained, the variables that had been excluded after the univariate analysis were added one by one, repeating the Poisson regression analysis to identify the variables that could contribute to the model.</p>
				<p>We also evaluated the multicollinearity between independent variables. The multicollinearity threshold was defined as a tolerance indicator with values less than 0.40.</p>
				<p>In addition, p&lt;0.05 was considered significant. The analyses were performed in the SAS 9.4 application.</p>
			</sec>
		</sec>
		<sec sec-type="results">
			<title>Results</title>
			<p>Among the 38 patients, 22 (58%) had pulmonary congestion with ReDS ≥ 35%, and 16 did not have congestion (patients with ReDS &lt; 35%). <xref ref-type="table" rid="t1">Tables 1</xref> (qualitative variables) and <xref ref-type="table" rid="t2">2</xref> (quantitative variables) describe the characteristics of the patient sample. <xref ref-type="table" rid="t3">Table 3</xref> compares the groups with ReDS ≥ 35% and &lt; 35% as to systemic and pulmonary congestion parameters. REDs&gt;35% group was older than REDs &lt; 35%, ≥ 35% group (pulmonary congestion). Although the mean number of B-lines was higher in the ReDS ≥35% group than in the ReDS &lt; 35% group, no statistical significance was found. The remaining parameters showed no differences.</p>
			<p>
				<table-wrap id="t1">
					<label>Table 1</label>
					<caption>
						<title>– Categorical variables (n = 38)</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead>
							<tr>
								<th align="left">Variables</th>
								<th>Frequency (n)</th>
								<th>Percentage (%)</th>
							</tr>
						</thead>
						<tbody>
							<tr>
								<td><bold>ReDS</bold></td>
								<td> </td>
								<td> </td>
							</tr>
							<tr>
								<td>&lt;35%</td>
								<td align="center">16</td>
								<td align="center">42%</td>
							</tr>
							<tr>
								<td>≥35%</td>
								<td align="center">22</td>
								<td align="center">58%</td>
							</tr>
							<tr>
								<td><bold>Gender</bold></td>
								<td> </td>
								<td> </td>
							</tr>
							<tr>
								<td>Female</td>
								<td align="center">17</td>
								<td align="center">45</td>
							</tr>
							<tr>
								<td>Male</td>
								<td align="center">21</td>
								<td align="center">55</td>
							</tr>
							<tr>
								<td><bold>Mitral regurgitation</bold></td>
								<td> </td>
								<td> </td>
							</tr>
							<tr>
								<td>None</td>
								<td align="center">2</td>
								<td align="center">5.3</td>
							</tr>
							<tr>
								<td>Mild</td>
								<td align="center">7</td>
								<td align="center">18.4</td>
							</tr>
							<tr>
								<td>Moderate</td>
								<td align="center">12</td>
								<td align="center">31.6</td>
							</tr>
							<tr>
								<td>Severe</td>
								<td align="center">17</td>
								<td align="center">44.7</td>
							</tr>
							<tr>
								<td><bold>Tricuspid regurgitation</bold></td>
								<td> </td>
								<td> </td>
							</tr>
							<tr>
								<td>None</td>
								<td align="center">4</td>
								<td align="center">10.5</td>
							</tr>
							<tr>
								<td>Mild</td>
								<td align="center">18</td>
								<td align="center">47.4</td>
							</tr>
							<tr>
								<td>Moderate</td>
								<td align="center">8</td>
								<td align="center">21.1</td>
							</tr>
							<tr>
								<td>Severe</td>
								<td align="center">8</td>
								<td align="center">21.1</td>
							</tr>
							<tr>
								<td><bold>Etiology of cardiomyopathy</bold></td>
								<td> </td>
								<td> </td>
							</tr>
							<tr>
								<td>Idiopathic</td>
								<td align="center">26</td>
								<td align="center">68.4</td>
							</tr>
							<tr>
								<td>Chagas</td>
								<td align="center">9</td>
								<td align="center">23.6</td>
							</tr>
							<tr>
								<td>Ischemic</td>
								<td align="center">3</td>
								<td align="center">7.8</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN1">
							<p>ReDS: Remote Dielectric Sensing.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
			</p>
			<p>
				<table-wrap id="t2">
					<label>Table 2</label>
					<caption>
						<title>– Continuous variables</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup>
							<col/>
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead>
							<tr>
								<th scope="col">Parameters</th>
								<th scope="col">Mean</th>
								<th scope="col">SD</th>
								<th scope="col">Minimum</th>
								<th scope="col">Maximum</th>
							</tr>
						</thead>
						<tbody>
							<tr>
								<td>Age (years)</td>
								<td align="center">63.2</td>
								<td align="center">12.4</td>
								<td align="center">26</td>
								<td align="center">81</td>
							</tr>
							<tr>
								<td>Systolic blood pressure (mmHg)</td>
								<td align="center">112.8</td>
								<td align="center">21.4</td>
								<td align="center">70</td>
								<td align="center">160</td>
							</tr>
							<tr>
								<td>Diastolic blood pressure (mmHg)</td>
								<td align="center">72.5</td>
								<td align="center">14.4</td>
								<td align="center">50</td>
								<td align="center">100</td>
							</tr>
							<tr>
								<td>BSA (m<sup>2</sup>)</td>
								<td align="center">1.8</td>
								<td align="center">0.2</td>
								<td align="center">1.41</td>
								<td align="center">2.3</td>
							</tr>
							<tr>
								<td>BMI (kg/m<sup>2</sup>)</td>
								<td align="center">29.5</td>
								<td align="center">8.1</td>
								<td align="center">16.5</td>
								<td align="center">55.7</td>
							</tr>
							<tr>
								<td>LV diastolic diameter (mm)</td>
								<td align="center">66.5</td>
								<td align="center">7.9</td>
								<td align="center">55</td>
								<td align="center">84</td>
							</tr>
							<tr>
								<td>Simpson's LV EF (%)</td>
								<td align="center">23.9</td>
								<td align="center">6.7</td>
								<td align="center">15</td>
								<td align="center">40</td>
							</tr>
							<tr>
								<td>LV mass index (g/m<sup>2</sup>)</td>
								<td align="center">126.5</td>
								<td align="center">39.4</td>
								<td align="center">69</td>
								<td align="center">246</td>
							</tr>
							<tr>
								<td>LA volume index (mL/m<sup>2</sup>)</td>
								<td align="center">65.1</td>
								<td align="center">23.4</td>
								<td align="center">31</td>
								<td align="center">158</td>
							</tr>
							<tr>
								<td>RA volume index (mL/m<sup>2</sup>)</td>
								<td align="center">48.9</td>
								<td align="center">32.9</td>
								<td align="center">14</td>
								<td align="center">172</td>
							</tr>
							<tr>
								<td>RV basal diameter (mm)</td>
								<td align="center">40.9</td>
								<td align="center">9.3</td>
								<td align="center">20</td>
								<td align="center">61</td>
							</tr>
							<tr>
								<td>RV lateral annular tissue velocity</td>
								<td align="center">8.2</td>
								<td align="center">2.6</td>
								<td align="center">4</td>
								<td align="center">16</td>
							</tr>
							<tr>
								<td>TAPSE (mmHg)</td>
								<td align="center">14.5</td>
								<td align="center">4.6</td>
								<td align="center">4</td>
								<td align="center">26</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN2">
							<p>SD: standard deviation; LV: left ventricle; RV: right ventricle; LA: left atrium; RA: right atrium; TAPSE: tricuspid annular plane systolic excursion; BSA: body surface area; BMI: body mass index; EF: ejection fraction.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
			</p>
			<p>
				<table-wrap id="t3">
					<label>Table 3</label>
					<caption>
						<title>– Comparison between REDs ≥35% and REDs &lt;35% groups</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup>
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead>
							<tr>
								<th align="left" rowspan="2">Parameters</th>
								<th colspan="2">ReDS</th>
								<th rowspan="2">p-value</th>
							</tr>
							<tr>
								<th>&lt; 35%</th>
								<th>≥ 35%</th>
							</tr>
						</thead>
						<tbody>
							<tr>
								<td><bold>Age (years)</bold></td>
								<td align="center">59±14.5</td>
								<td align="center">67±8.3</td>
								<td align="center">0.03</td>
							</tr>
							<tr>
								<td><bold>LVOT VTI</bold></td>
								<td align="center">12.5 ± 4.8</td>
								<td align="center">12.8 ± 4.1</td>
								<td align="center">0.82</td>
							</tr>
							<tr>
								<td><bold>Mean E/e'</bold></td>
								<td align="center">16.1 ± 7.2</td>
								<td align="center">17.1 ± 7.1</td>
								<td align="center">0.69</td>
							</tr>
							<tr>
								<td><bold>IVC (mm)</bold></td>
								<td align="center">17.4 ± 7.3</td>
								<td align="center">17.95 ± 4.6</td>
								<td align="center">0.76</td>
							</tr>
							<tr>
								<td><bold>Vena cava collapse (%)</bold></td>
								<td align="center">42.5 ± 41.5</td>
								<td align="center">33.36 ± 25.4</td>
								<td align="center">0.89</td>
							</tr>
							<tr>
								<td><bold>RA estimated blood pressure (mmHg)</bold></td>
								<td align="center">6.6 ± 5.3</td>
								<td align="center">7.23 ± 4.41</td>
								<td align="center">0.44</td>
							</tr>
							<tr>
								<td><bold>NT-proBNP (pcg/mL)</bold></td>
								<td align="center">4311.4 ± 3289.7</td>
								<td align="center">4267.7 ± 4136.9</td>
								<td align="center">0.97</td>
							</tr>
							<tr>
								<td><bold>B-lines (units)</bold></td>
								<td align="center">7.19 ± 4.43</td>
								<td align="center">9.82 ± 7.43</td>
								<td align="center">0.18</td>
							</tr>
							<tr>
								<td><bold>Dizziness</bold></td>
								<td> </td>
								<td> </td>
								<td align="center">0.97</td>
							</tr>
							<tr>
								<td>No</td>
								<td align="center">11 (42.31)</td>
								<td align="center">15 (57.69)</td>
								<td> </td>
							</tr>
							<tr>
								<td>Yes</td>
								<td align="center">5 (41.67)</td>
								<td align="center">7 (58.33)</td>
								<td> </td>
							</tr>
							<tr>
								<td><bold>Paroxysmal nocturnal dyspnea</bold></td>
								<td> </td>
								<td> </td>
								<td align="center">0.19</td>
							</tr>
							<tr>
								<td>No</td>
								<td align="center">12 (50.00)</td>
								<td align="center">12 (50.00)</td>
								<td> </td>
							</tr>
							<tr>
								<td>Yes</td>
								<td align="center">4 (28.57)</td>
								<td align="center">10 (71.43)</td>
								<td> </td>
							</tr>
							<tr>
								<td><bold>Jugular vein distention</bold></td>
								<td> </td>
								<td> </td>
								<td align="center">0.11</td>
							</tr>
							<tr>
								<td>No</td>
								<td align="center">4 (26.67)</td>
								<td align="center">11 (73.33)</td>
								<td> </td>
							</tr>
							<tr>
								<td>Yes</td>
								<td align="center">12 (52.17)</td>
								<td align="center">11 (47.83)</td>
								<td> </td>
							</tr>
							<tr>
								<td><bold>LEE</bold></td>
								<td> </td>
								<td> </td>
								<td align="center">0.08</td>
							</tr>
							<tr>
								<td>No</td>
								<td align="center">11 (50.00)</td>
								<td align="center">9 (45.00)</td>
								<td> </td>
							</tr>
							<tr>
								<td>Yes</td>
								<td align="center">5 (27.78)</td>
								<td align="center">13 (72.22)</td>
								<td> </td>
							</tr>
							<tr>
								<td><bold>Hepatomegaly</bold></td>
								<td> </td>
								<td> </td>
								<td align="center">0.57</td>
							</tr>
							<tr>
								<td>No</td>
								<td align="center">8 (38.10)</td>
								<td align="center">13 (61.90)</td>
								<td> </td>
							</tr>
							<tr>
								<td>Yes</td>
								<td align="center">8 (47.06)</td>
								<td align="center">9 (52.94)</td>
								<td> </td>
							</tr>
							<tr>
								<td><bold>Troponin</bold></td>
								<td> </td>
								<td> </td>
								<td align="center">0.24</td>
							</tr>
							<tr>
								<td>Abnormal (≥0.04 ng/mL)</td>
								<td align="center">11 (50.00)</td>
								<td align="center">11 (50.00)</td>
								<td> </td>
							</tr>
							<tr>
								<td>Normal (&lt;0.04 ng/mL)</td>
								<td align="center">5 (31.25)</td>
								<td align="center">11 (68.75)</td>
								<td> </td>
							</tr>
							<tr>
								<td><bold>Creatinine</bold></td>
								<td> </td>
								<td> </td>
								<td align="center">0.66</td>
							</tr>
							<tr>
								<td>Normal (&lt;1.4 mg/dL)</td>
								<td align="center">8 (42.11)</td>
								<td align="center">11 (57.89)</td>
								<td> </td>
							</tr>
							<tr>
								<td>Mild abnormality (1.4–2.0 mg/dL).</td>
								<td align="center">5 (35.71)</td>
								<td align="center">9 (64.29)</td>
								<td> </td>
							</tr>
							<tr>
								<td>Moderate abnormality (&gt;2.1 mg/dL)</td>
								<td align="center">3 (60.00)</td>
								<td align="center">2 (40.00)</td>
								<td> </td>
							</tr>
							<tr>
								<td><bold>NYHA FC HF</bold></td>
								<td> </td>
								<td> </td>
								<td align="center">0.82</td>
							</tr>
							<tr>
								<td>I</td>
								<td align="center">0 (0.00)</td>
								<td align="center">2 (100.00)</td>
								<td> </td>
							</tr>
							<tr>
								<td>II</td>
								<td align="center">8 (47.06)</td>
								<td align="center">9 (52.94)</td>
								<td> </td>
							</tr>
							<tr>
								<td>III</td>
								<td align="center">7 (41.18)</td>
								<td align="center">10 (58.82)</td>
								<td> </td>
							</tr>
							<tr>
								<td>IV</td>
								<td align="center">1 (50.00)</td>
								<td align="center">1 (50.00</td>
								<td> </td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN3">
							<p>ReDS: Remote Dielectric Sensing; LVOT VTI: left ventricular outflow tract velocity time integral; E/e’: ratio between the mitral inflow E velocity and the mean lateral and medial annular tissue Doppler; RA: right atrium; NT-proBNP: N-terminal pro-B-type natriuretic peptide; LEE: lower extremity edema; IVC: inferior vena cava; NYHA FC HF: New York Heart Association Functional Class of Heart Failure.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
			</p>
			<p>Clinical data — such as BSA, gender, dizziness, paroxysmal nocturnal dyspnea, and LEE —, NT-proBNP, and TTE measurements — such as LAV, LVOT VTI, mean E/e’ ratio, RV peak lateral tricuspid annular systolic velocity (RV S’), TAPSE, IVC analysis, and B-line count — were compared with Poisson models with robust variance adjusted for ReDS ≥35%. In the multivariate analysis, these were the variables associated with ReDS≥35% and their adjusted prevalence ratio (aPR): BSA: 8.7 (2.7; 27.8), p = 0.003; RV S’: 1.12 (1.00; 1.04), p = 0.03; B-lines: 1.02 (1.00; 1.04), p = 0.04; and LEE: 1.56 (1.00; 2.57), p = 0.04 (<xref ref-type="table" rid="t4">Table 4</xref>).</p>
			<p>
				<table-wrap id="t4">
					<label>Table 4</label>
					<caption>
						<title>– Multivariate analysis with adjusted variance for ReDS≥35%</title>
					</caption>
					<table frame="hsides" rules="groups">
						<colgroup>
							<col/>
							<col/>
							<col/>
							<col/>
							<col/>
						</colgroup>
						<thead>
							<tr>
								<th align="left" rowspan="2">Variables</th>
								<th colspan="2">Crude PR</th>
								<th colspan="2">Adjusted PR<sup><bold>*</bold></sup></th>
							</tr>
							<tr>
								<th>PR (95%CI)</th>
								<th>p-value</th>
								<th>PR (95%CI)</th>
								<th>p-value</th>
							</tr>
						</thead>
						<tbody>
							<tr>
								<td><bold>Gender</bold></td>
								<td> </td>
								<td align="center">0.0862</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td>Female</td>
								<td align="center">1</td>
								<td align="center">-</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td>Male</td>
								<td align="center">1.73 (0.92; 3.25)</td>
								<td align="center">0.09</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>Systolic blood pressure</bold></td>
								<td align="center">1.01 (1.00; 1.03)</td>
								<td align="center">0.05</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>Diastolic blood pressure</bold></td>
								<td align="center">1.01 (0.99; 1.03)</td>
								<td align="center">0.16</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>BSA</bold></td>
								<td align="center">5.41 (2.2; 13.6)</td>
								<td align="center">0.0003</td>
								<td align="center">8.67 (2.71; 27.82)</td>
								<td align="center">0.0003</td>
							</tr>
							<tr>
								<td><bold>BMI</bold></td>
								<td align="center">1.02 (0.99; 1.06)</td>
								<td align="center">0.25</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>End-diastolic diameter</bold></td>
								<td align="center">1.02 (0.99; 1.05)</td>
								<td align="center">0.23</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>LA volume index</bold></td>
								<td align="center">1.00 (1.00; 1.01)</td>
								<td align="center">0.34</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>RV S'</bold></td>
								<td align="center">1.07 (0.99; 1.20)</td>
								<td align="center">0.06</td>
								<td align="center">1.12 (1.01; 1.24)</td>
								<td align="center">0.0262</td>
							</tr>
							<tr>
								<td><bold>TAPSE</bold></td>
								<td align="center">1.03 (0.97; 1.09)</td>
								<td align="center">0.36</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>LVOT VTI</bold></td>
								<td align="center">1.01 (0.94; 1.07)</td>
								<td align="center">0.82</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>Mean E/e'</bold></td>
								<td align="center">1.01 (0.97; 1.05)</td>
								<td align="center">0.68</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>IVC</bold></td>
								<td align="center">1.01 (0.96; 1.06)</td>
								<td align="center">0.78</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>Vena cava collapse</bold></td>
								<td align="center">1.00 (0.99; 1.01)</td>
								<td align="center">0.43</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>RA estimated blood pressure</bold></td>
								<td align="center">1.01 (0.95; 1.07)</td>
								<td align="center">0.70</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>NT-proBNP</bold></td>
								<td align="center">1.00 (1.00; 1.00)</td>
								<td align="center">0.97</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>B-lines</bold></td>
								<td align="center">1.03 (0.99; 1.06)</td>
								<td align="center">0.09</td>
								<td align="center">1.02 (1.00; 1.04)</td>
								<td align="center">0.0403</td>
							</tr>
							<tr>
								<td><bold>Dizziness/BP drop</bold></td>
								<td> </td>
								<td align="center">0.97</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td>No</td>
								<td align="center">1</td>
								<td align="center">-</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td>Yes</td>
								<td align="center">1.01 (0.57; 1.81)</td>
								<td align="center">0.97</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>Paroxysmal nocturnal dyspnea</bold></td>
								<td> </td>
								<td align="center">0.17</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td>No</td>
								<td align="center">1</td>
								<td align="center">-</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td>Yes</td>
								<td align="center">1.43 (0.85; 2.40)</td>
								<td align="center">0.18</td>
								<td align="center">-</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td><bold>LEE</bold></td>
								<td> </td>
								<td align="center">0.09</td>
								<td> </td>
								<td align="center">0.0479</td>
							</tr>
							<tr>
								<td>No</td>
								<td align="center">1</td>
								<td align="center">-</td>
								<td align="center">1</td>
								<td align="center">-</td>
							</tr>
							<tr>
								<td>Yes</td>
								<td align="center">1.60 (0.91; 2.82)</td>
								<td align="center">0.09</td>
								<td align="center">1.56 (1.00; 2.57)</td>
								<td align="center">0.0479</td>
							</tr>
						</tbody>
					</table>
					<table-wrap-foot>
						<fn id="TFN4">
							<p>ReDS: Remote Dielectric Sensing; PR: prevalence ratio; 95%CI: 95% confidence interval; LA: left atrium; RV S’: right ventricle tricuspid annular systolic velocity by tissue Doppler imaging; TAPSE: tricuspid annular plane systolic excursion; LVOT VTI: left ventricular outflow tract velocity time integral; E/e’: ratio between the mitral inflow E velocity and the mean lateral and medial annular tissue Doppler; RA: right atrium; NT-proBNP: N-terminal pro-B-type natriuretic peptide; BP: blood pressure; LEE: lower extremity edema; BSA: body surface area; BMI: body mass index; IVC: inferior vena cava.</p>
						</fn>
					</table-wrap-foot>
				</table-wrap>
			</p>
			<p>NT-proBNP was similar and high in both groups, with no correlation with ReDS (4311 ± 3289 mg/dL for ReDS &lt;35% and 4267 ± 4136 mg/dL for ReDS ≥35%, p = 0.97) (<xref ref-type="table" rid="t4">Table 4</xref>).</p>
			<p>The B-line count variability among observers was assessed based on stored images from 20 patients, with a 97% correlation coefficient.</p>
		</sec>
		<sec sec-type="discussion">
			<title>Discussion</title>
			<p>The main finding of this pilot study of patients with HFrEF and difficult therapeutic volume management was the significant correlation between LUS B-lines and a high-accuracy device for the detection of pulmonary congestion (ReDS). Thus, LUS can be adopted in the outpatient management of pulmonary congestion, reducing the costs of frequent hospitalizations and optimizing the use of diuretics.</p>
			<p>ReDS has an excellent correlation with chest computed tomography for the detection of pulmonary congestion, using software that analyzes the pulmonary density of patients with decompensated HFrEF and normal volunteers,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> as well as those with pulmonary capillary pressure by an invasive method.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> However, no studies have compared the number of B-lines in outpatient LUS among patients with HFrEF and ReDS as the gold standard.</p>
			<p>The use of LUS to evaluate pulmonary congestion is well established. A multicenter study conducted by the Study and Research Center of the Italian Society of Emergency Medicine (<italic>Società Italiana di Medicina di Emergenza Urgenza</italic> — SIMEU) found that clinical evaluation associated with the detection of B-lines in LUS had a 97% accuracy in detecting pulmonary congestion, a number that exceeded even that of NT-proBNP, which presented only 62% accuracy.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> These findings agree with those of our study, with B-lines correlated with ReDS≥35%, and NT-proBNP, although high in both groups, showing no correlation with ReDS.</p>
			<p>The increase in B-lines identified in LUS, in addition to improve diagnose the cause of dyspnea in the emergency department,<sup><xref ref-type="bibr" rid="B22">22</xref></sup> is associated with a higher number of hospitalizations<sup><xref ref-type="bibr" rid="B23">23</xref></sup> and worse prognosis in post-myocardial infarction patients.<sup><xref ref-type="bibr" rid="B24">24</xref></sup> Miglioranza et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> revealed that the finding of 15 B-lines in LUS indicated the possibility of imminent decompensation among patients in outpatient follow-up, but did not compare the congestion results from LUS with any gold standard. Our study found that, compared to a gold standard (ReDS), B-lines were correlated with increased pulmonary congestion in outpatients with HFrEF and difficult volume control.</p>
			<p>Regarding systemic congestion parameters, we detected a correlation with ReDS≥35% only in the evaluation of the longitudinal function of RV S’ by tissue Doppler imaging and in the finding of LEE on physical examination. ReDS was not expected to correlate with systemic congestion parameters, since it measures the amount of extravascular lung fluid. Nonetheless, patients with greater pulmonary congestion and RV dysfunction might present higher systemic congestion and, consequently, LEE.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup></p>
			<p>BSA had a good correlation with ReDS, as the calculation used by the device depends on the patient’s weight and height.<sup><xref ref-type="bibr" rid="B11">11</xref></sup></p>
			<sec>
				<title>Potential limitations and strengths of the study</title>
				<p>The main study limitation is the small number of patients, all recruited from a single center. Another possible limitation was the lack of invasive measures that could directly detect filling pressures for comparison with the number of B-lines and ReDS.</p>
				<p>Given the significant correlation of B-lines with ReDS≥35%, despite the reduced number of individuals included in the study, this result is the main strength of the research, due to the high sensitivity of B-line detection by LUS among patients with difficult volume control.</p>
			</sec>
		</sec>
		<sec sec-type="conclusions">
			<title>Conclusions</title>
			<p>In this pilot study, LUS presented a good correlation with pulmonary congestion measured by a high-accuracy device (ReDS) and can be a particularly useful tool in the outpatient management of patients with HFrEF, reducing hospitalizations and improving blood volume control among these individuals.</p>
			<p>Regarding systemic congestion parameters, only RV S’ was significant, indicating that patients with greater RV dysfunction have concomitant pulmonary congestion and systemic congestion.</p>
		</sec>
	</body>
	<back>
		<ack>
			<title>Acknowledgments</title>
			<p>The authors thank Professor Eduardo Freitas da Silva for the outstanding work in correcting and guiding the statistical analysis.</p>
		</ack>
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		<fn-group>
			<fn fn-type="other">
				<p>Study Association</p>
				<p>This study is not associated with any thesis or dissertation work.</p>
			</fn>
			<fn fn-type="other">
				<p>Ethics Approval and Consent to Participate</p>
				<p>This study was approved by the Ethics Committee of the Instituto Dante Pazzanese under the protocol number 532248210.0000.5462. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
			</fn>
		</fn-group>
		<fn-group>
			<fn fn-type="supported-by">
				<p>Sources of Funding: There were no external funding sources for this study.</p>
			</fn>
		</fn-group>
	</back>
	<sub-article article-type="translation" id="TRpt" xml:lang="pt">
		<front-stub>
			<article-id pub-id-type="doi">10.36660/abcimg.20230027</article-id>
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					<role>Concepção e desenho da pesquisa</role>
					<role>obtenção de dados</role>
					<role>análise e interpretação dos dados e revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
				<contrib contrib-type="author">
					<name>
						<surname>Assef</surname>
						<given-names>Jorge Eduardo</given-names>
					</name>
					<role>Concepção e desenho da pesquisa</role>
					<role>análise e interpretação dos dados e revisão crítica do manuscrito quanto ao conteúdo intelectual importante</role>
					<role>redação do manuscrito</role>
					<xref ref-type="aff" rid="aff1002"><sup>1</sup></xref>
				</contrib>
			</contrib-group>
			<aff id="aff1002">
				<label>1</label>
				<country country="BR">Brasil</country>
				<institution content-type="original">Instituto Dante Pazzanese de Cardiologia, São Paulo, SP – Brasil</institution>
			</aff>
			<aff id="aff2002">
				<label>2</label>
				<country country="BR">Brasil</country>
				<institution content-type="original">Instituto de Cardiologia e Transplante do Distrito Federal, Brasília, DF – Brasil</institution>
			</aff>
			<author-notes>
				<corresp id="c01002"> Correspondência: Maria Estefânia Bosco Otto • Instituto de Cardiologia do Distrito Federal (ICDF): Ecocardiograma. SQSW 301. Bloco F. Ap 508. CEP: 70673-106. Brasília, DF – Brasil E-mail: mariaestefaniaotto@gmail.com </corresp>
				<fn fn-type="edited-by">
					<p>Editor responsável pela revisão: Daniela do Carmo Rassi Frota</p>
				</fn>
				<fn fn-type="conflict">
					<p>Potencial Conflito de Interesse</p>
					<p>Declaro não haver conflito de interesses pertinentes.</p>
				</fn>
			</author-notes>
			<abstract>
				<title>Resumo</title>
				<sec>
					<title>Introdução</title>
					<p> A avaliação de congestão pulmonar ambulatorial em pacientes com insuficiência cardíaca com fração de ejeção reduzida (ICFER) pode minimizar internações por descompensação e otimizar o uso de diuréticos.</p>
				</sec>
				<sec>
					<title>Objetivo</title>
					<p> Comparar o dispositivo dielétrico remoto (DDR), equipamento validado para detectar líquido extravascular pulmonar, com parâmetros clínicos, medidas de ecocardiograma transtorácico (ETT) e ultrassom de pulmão (ULSP).</p>
				</sec>
				<sec>
					<title>Métodos</title>
					<p> Incluímos 38 pacientes do ambulatório de miocardiopatias (63±12 anos; 21 homens). Todos foram submetidos, num período de 24 horas, à avaliação clínica com descrição de dispneia paroxística noturna, edema de membros inferiores (EMI), presença de tonturas; avaliação laboratorial de NT-ProBNP; avaliação pelo DDR e ETT com análise de parâmetros de congestão sistêmica pela veia cava inferior, função do ventrículo direito e de congestão pulmonar, como a avaliação das pressões de enchimento por meio E/e’ médio e volume indexado do átrio esquerdo. O ULSP foi realizado com o protocolo de 8 quadrantes anteriores, com contagem de linhas B em um ciclo respiratório.</p>
				</sec>
				<sec>
					<title>Resultados</title>
					<p> 22 pacientes apresentavam DDR ≥ 35% (congestão pulmonar) e 16 pacientes DDR &lt; 35%. Parâmetros clínicos e ecocardiográficos foram comparados com o DDR ≥ 35%. Na análise multivariada, as variáveis superfície corpórea (SC), linhas B e EMI se associaram a DDR ≥ 35%. NT-ProBNP foi semelhante e elevado em ambos os grupos.</p>
				</sec>
				<sec>
					<title>Conclusões</title>
					<p> O acompanhamento ambulatorial de ICFER para controle volêmico pode ser sensibilizado pela presença de linhas B no ULSP, que apresenta boa correlação com DDR ≥ 35%. NT-ProBNP não foi capaz de diferenciar pacientes com maior grau de congestão detectado pelo DDR.</p>
				</sec>
			</abstract>
			<kwd-group xml:lang="pt">
				<kwd>Ultrassonografia</kwd>
				<kwd>Pulmão</kwd>
				<kwd>Insuficiência Cardíaca</kwd>
			</kwd-group>
		</front-stub>
		<body>
			<sec sec-type="intro">
				<title>Introdução</title>
				<p>A avaliação ambulatorial do estado volêmico de pacientes com insuficiência cardíaca com fração de ejeção reduzida (ICFER), independentemente da etiologia, é complexa e requer a integração de sinais clínicos e laboratoriais.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup> A detecção precoce de aumento de volemia por métodos invasivos foi capaz de melhorar a otimização do tratamento farmacológico, evitar internações e complicações como insuficiência renal e aumento inapropriado de diuréticos.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> No entanto, para controle ambulatorial de pacientes com ICFER, não podemos utilizar métodos invasivos, sendo necessária a análise de parâmetros clínicos associados a métodos de imagem, como o ecocardiograma<sup><xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr" rid="B6">6</xref></sup> e ultrassom de pulmão (ULSP).<sup><xref ref-type="bibr" rid="B7">7</xref>-<xref ref-type="bibr" rid="B9">9</xref></sup></p>
				<p>Recentemente, uma nova tecnologia de avaliação de volemia,<sup><xref ref-type="bibr" rid="B10">10</xref></sup> o chamado REDS (<italic>Remote Dieletric Sensing</italic>: Sensible Medical Inovations, Ltd, Klar Neter, Israel), a qual será denominada dispositivo dielétrico remoto (DDR), tem mostrado resultados promissores de monitoramento de líquido extravascular pulmonar, já com validação pela tomografia.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> Entretanto, o ULSP não foi comparado com o DDR realizado ambulatorialmente para controle de pacientes com ICFER e difícil controle terapêutico. A vantagem da utilização do ULSP agregado ao exame físico e análise laboratorial é seu baixo custo, fácil treinamento e boa reprodutibilidade.<sup><xref ref-type="bibr" rid="B8">8</xref>,<xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup></p>
				<p>Desta forma, o objetivo deste estudo foi comparar o USLP para diagnóstico de congestão pulmonar em pacientes ambulatoriais com ICFER de difícil controle terapêutico com o DDR como padrão ouro de análise de líquido extravascular pulmonar. Adicionalmente, parâmetros clínicos, ecocardiográficos e laboratoriais foram agregados nesta análise para sensibilizar a detecção do equilíbrio volêmico sistêmico deste grupo de pacientes.</p>
			</sec>
			<sec sec-type="methods">
				<title>Métodos</title>
				<p>Neste estudo piloto de coorte prospectivo, realizado de dezembro de 2021 a fevereiro de 2022, incluímos pacientes acima de 18 anos selecionados do ambulatório de miocardiopatias do Instituto Dante Pazzanese de Cardiologia (IDPC) que fazem acompanhamento seriado no ambulatório de volemia, por serem portadores de ICFER, com dificuldade de controle volêmico. O consentimento informado foi obtido de cada paciente e o protocolo do estudo está em conformidade com as diretrizes éticas da Declaração de Helsinki de 1975. O protocolo foi aprovado pelo Comitê de Pesquisa do IDPC sob o Certificado de Apresentação de Ética número 53224821.0.0000.5462.</p>
				<sec>
					<title>Casuística e desenho do estudo</title>
					<p>Os pacientes com ICFER e dificuldade de controle volêmico são avaliados em um ambulatório específico do IDPC para minimizar complicações que possam ocorrer pelo uso de altas doses de diuréticos e retornos mais precoces. Dessa forma, pode-se concentrar a inclusão de pacientes nestes dias para que o DDR pudesse ser disponibilizado uma vez por semana para o IDPC e as avaliações de ecocardiograma focado para análise de parâmetros relacionados à volemia e ULSP para avaliação de linhas “B” fossem realizadas no mesmo dia ou na manhã seguinte. Os pesquisadores responsáveis pelas avaliações de ultrassom não tinham conhecimento do resultado de volemia obtido pelo DDR.</p>
					<p>Foram incluídos 38 pacientes de forma consecutiva com ICFER de diversas etiologias. Realizou-se a inclusão de acordo com a disponibilidade do DDR e da possibilidade de realizar o ecocardiograma e ULSP no tempo adequado.</p>
				</sec>
				<sec>
					<title>Avaliação clínica</title>
					<p>Os pacientes selecionados foram avaliados em consulta ambulatorial de rotina. Elegeu-se os seguintes dados clínicos para comparação com o estado volêmico: peso, superfície corporal, índice massa corporal (IMC), edema de membros inferiores (EMI) e classe funcional pela <italic>New York Heart Association.</italic><sup><xref ref-type="bibr" rid="B1">1</xref></sup> Todos os exames clínicos foram supervisionados e conferidos por um cardiologista clínico experiente.</p>
				</sec>
				<sec>
					<title>Avaliação laboratorial</title>
					<p>Em sequência à avaliação clínica, procedeu-se a coleta de NT-ProBNP. A coleta e análise dos exames de sangue foi realizada pelo laboratório de análises clínicas do IDPC. A padronização da coleta, os métodos e os equipamentos de análise estão de acordo com a rotina do serviço.</p>
				</sec>
				<sec>
					<title>Utilização do DDR</title>
					<p>Após a coleta de exames laboratoriais, os voluntários foram submetidos a avaliação pelo DDR (Sensible Medical Inovations, Ltd, Klar Neter, Israel). A tecnologia do DDR consiste em um radar em miniatura, que emprega sinais eletromagnéticos de baixa potência emitidos para o corpo.<sup><xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup> Pode ser utilizado na avaliação do paciente por meio de colete aplicado ao tórax (<xref ref-type="fig" rid="f01002">Figura 1</xref>). Dois sensores embutidos no colete são fixados ao corpo: um anteriormente no peito, à direita, e outro, posteriormente, nas costas. Cada sensor é capaz de transmitir e receber o feixe de ondas eletromagnéticas que atravessa o pulmão. O sinal refletido é analisado e traduz as propriedades dielétricas do tecido pulmonar entre os sensores. Uma vez que a água tem um coeficiente dielétrico muito alto, os coeficientes dielétricos dos tecidos são determinados predominantemente por seu conteúdo de fluido.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> O pulmão humano saudável (para uma pessoa média de 70 kg) contém 450 a 500 ml de sangue. O compartimento extravascular normalmente tem outros 250 a 700 ml de fluido. Uma vez que o volume de ar pulmonar total normal seja de 1,8 a 2,2 l, considerando um volume corrente de 500 ml, pode-se estimar que o conteúdo normal de líquido intratorácico varia entre 20 e 34% do volume total.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> Confirmou-se este intervalo por medições de densidade realizadas por diferentes tecnologias de imagem quantitativa.<sup><xref ref-type="bibr" rid="B11">11</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup></p>
					<p>
						<fig id="f01002">
							<label>Figura 1</label>
							<caption>
								<title>– DDR. Imagem cedida pela empresa fabricante do DDR (Remote Dieletric Sensing: Sensible Medical Inovations, Ltd, Klar Neter, Israel).</title>
							</caption>
							<graphic xlink:href="2675-312X-dic-36-02-e20230027-gf01-pt.tif"/>
						</fig>
					</p>
					<p>As medições do DDR foram realizadas por profissionais treinados na utilização do dispositivo. Estes pacientes permaneceram sentados com o DDR por quarenta e cinco segundos em repouso, após os quais o dispositivo forneceu automaticamente o porcentual de líquido torácico. O valor normal é definido como até 34%, possível hipervolemia de 35-50% e hipervolemia significativa acima de 50% e abaixo de 20% hipovolemia (dados do fabricante).</p>
				</sec>
				<sec>
					<title>ULSP</title>
					<p>O ULSP foi realizado no equipamento GE Vivid E95 (GE Health Care, Norway), pelo protocolo de oito segmentos anteriores com transdutor setorial de 2-5 Mhz e ajuste do equipamento de ecocardiografia para o modo “abdominal”. As aquisições de imagem ocorreram em 6 segundos, permitindo avaliar um ciclo respiratório. Este protocolo é denominado protocolo BLUE (Bedside Lung Ultrasoud in Emergency),<sup><xref ref-type="bibr" rid="B12">12</xref>,<xref ref-type="bibr" rid="B17">17</xref>-<xref ref-type="bibr" rid="B19">19</xref></sup> com o paciente na posição de 45 graus de inclinação do tórax na maca. O objetivo do protocolo é a avaliação da presença de linhas “B”, artefatos que se formam no ULSP em consequência do aumento de líquido parenquimatoso e contagem em cada segmento em um ciclo respiratório (<xref ref-type="fig" rid="f02002">Figura 2</xref>).<sup><xref ref-type="bibr" rid="B19">19</xref></sup> O achado de mais de três linhas B em 2 quadrantes de cada hemitórax significa congestão em pacientes com ICFER. Optou-se por realizar a contagem total de linhas B em ambos hemitórax.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B19">19</xref></sup> Esta avaliação foi realizada por examinador treinado, sem conhecimento do quadro clínico do paciente ou dos resultados de exames laboratoriais e da volemia estimada pelo DDR. As imagens foram gravadas e arquivadas em mídia específica para análise de variabilidade da contagem de linhas B por outro profissional envolvido no estudo.</p>
					<p>
						<fig id="f02002">
							<label>Figura 2</label>
							<caption>
								<title>– Representação esquemática do protocolo BLUE (Bed Side Lung Ultrasound in Emergency). A) Análise do tórax anterior; B) Análise da região lateral utilizando a linha axilar posterior como referência.</title>
							</caption>
							<graphic xlink:href="2675-312X-dic-36-02-e20230027-gf02-pt.tif"/>
							<attrib>Modelo de localização dos pontos a serem avaliados com ULSP pelo protocolo BLUE. A) Utilizar as 2 mãos no hemitórax do paciente com o dedo mínimo superior logo abaixo da clavícula (linha preta acima do dedo mínimo), excluir os polegares e a região inferior da outra mão é posicionada ao nível da linha diafragmática (linha preta). O ponto denominado “BLUE superior” (ponto vermelho) está no meio da mão superior. O “ponto BLUE inferior” está no meio da palma inferior. Esses quatro pontos seguem aproximadamente a anatomia do pulmão e evitam a área cardíaca. B) O ponto da região do seio costo-frênico (ponto vermelho) é construído partindo da linha horizontal, continuando o ponto BLUE inferior, e a linha vertical, continuando a linha axilar posterior (linha preta). Para completar, pode-se adicionar um ponto superior entre a linha axilar posterior e anterior, no andar superior do tórax. Dessa forma, teremos 4 pontos em cada hemitórax. Imagem produzida por Dra. Maria Estefânia Bosco Otto.<sup>19</sup></attrib>
						</fig>
					</p>
				</sec>
				<sec>
					<title>Ecocardiograma</title>
					<p>O exame de ecocardiograma com medidas de avaliação da função biventricular e parâmetros específicos relacionados à volemia foi feito no mesmo momento do ULSP, no mesmo equipamento, modificando somente o modo de análise da imagem para “ecocardiograma adulto”, pelo mesmo profissional. Avaliaram-se os seguintes parâmetros do ventrículo esquerdo (VE): diâmetro sistólico, diastólico e fração de ejeção pelo método biplanar de Simpson (FE); integral da velocidade de fluxo da via de saída do VE (VTI VSVE); medidas integradas de função diastólica, tais como, velocidade da onda E mitral, velocidade da onda A mitral, relação E/A, Doppler tecidual do anel septal e lateral mitral para avaliação da velocidade da onda e’, relação E/e’ média, volume do átrio esquerdo e pressão sistólica da artéria pulmonar pelo Doppler contínuo da regurgitação tricúspide; função semiquantitativa do ventrículo direito com análise do TAPSE, velocidade sistólica do anel lateral tricúspide e avaliação subjetiva; avaliação da pressão do átrio direito (PAD) por meio de análise da veia cava inferior feita segundo as orientações da Sociedade Americana de Ecocardiografia.<sup><xref ref-type="bibr" rid="B20">20</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup></p>
					<p>As imagens de ecocardiograma foram gravadas e arquivadas em mídia específica.</p>
				</sec>
				<sec>
					<title>Análise estatística</title>
					<p>Para se comparar os parâmetros de imagem e clínicos entre pacientes com DDR &lt; 35% e pacientes com DDR ≥ 35%, foram empregados os testes de t de Student ou não paramétrico de Mann-Whitney para as variáveis quantitativas e os testes de qui-quadrado ou exato de qui-quadrado para as variáveis qualitativas.</p>
					<p>A avaliação de indicadores independentes de congestão pulmonar consistiu na comparação de parâmetros cardiológicos e clínicos e no ajuste de modelos de regressão de Poisson com variância robusta para o resultado de DDR ≥ 35% associada às variáveis epidemiológicas, de sinais vitais e antropométricas, de massa, volumes e função do VE, de função diastólica, do ventrículo direito, de veia cava inferior e de variáveis clínicas, empregando-se como medida de efeito a razão de prevalência e seus respectivos intervalos de confiança. A análise se deu em duas etapas: univariada e multivariada. Em ambas, razões de prevalência e seus respectivos intervalos de 95% de confiança foram calculados.</p>
					<p>Na análise univariada, verificou-se a associação entre cada variável independente e a ocorrência de resultado de DDR ≥ 35% e aquelas que apresentaram p &lt; 0,25 foram selecionadas para serem incluídas na análise multivariada. Nesta, construiu-se os modelos pela exclusão consecutiva de uma variável de cada modelo completo que apresentava o maior valor de p do teste de Wald, conforme descrito por Hosmer e Lemeshow e reajustando-se e verificando-se a estabilidade do modelo após a retirada de cada variável, de forma a obter um modelo mais parcimonioso e que melhor se ajustasse aos dados. Uma vez que o modelo final foi obtido, as variáveis que tinham sido excluídas após a análise univariada foram adicionadas ao modelo, uma a uma, repetindo a análise de regressão de Poisson para identificar as variáveis que poderiam dar uma contribuição ao modelo.</p>
					<p>A multicolinearidade entre as variáveis independentes foi avaliada. Considerou-se o limite da presença de multicolinearidade se o indicador de tolerância assume valores menores que 0,40.</p>
					<p>Ainda, considerou-se significativo p &lt; 0,05. As análises foram conduzidas pelo aplicativo SAS 9.4.</p>
				</sec>
			</sec>
			<sec sec-type="results">
				<title>Resultados</title>
				<p>Dos 38 pacientes, 22 (58%) apresentaram congestão pulmonar com DDR ≥ 35% e 16 sem congestão (pacientes com DDR &lt; 35%). As características da amostra de pacientes estão descritas nas <xref ref-type="table" rid="t1002">Tabelas 1</xref> (variáveis qualitativas) e <xref ref-type="table" rid="t2002">2</xref> (variáveis quantitativas). A comparação entre os grupos com DDR ≥ 35% e &lt; 35% em relação a parâmetros de congestão sistêmica e pulmonar está na <xref ref-type="table" rid="t3002">Tabela 3</xref>. A idade do grupo com DDR ≥ 35% (congestão pulmonar) foi maior que o grupo sem congestão. Apesar de a média da quantidade de linhas B ser maior no grupo DDR ≥ 35% em comparação ao grupo com DDR &lt; 35%, não houve significância estatística. Os demais parâmetros não apresentaram diferenças.</p>
				<p>
					<table-wrap id="t1002">
						<label>Tabela 1</label>
						<caption>
							<title>– Variáveis categóricas (n = 38)</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left">Variáveis</th>
									<th>Frequência (n)</th>
									<th>Porcentagem (%)</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td><bold>DDR</bold></td>
									<td> </td>
									<td> </td>
								</tr>
								<tr>
									<td>&lt; 35%</td>
									<td align="center">16</td>
									<td align="center">42%</td>
								</tr>
								<tr>
									<td>
										<underline>&gt;</underline>35 %</td>
									<td align="center">22</td>
									<td align="center">58%</td>
								</tr>
								<tr>
									<td><bold>Gênero</bold></td>
									<td> </td>
									<td> </td>
								</tr>
								<tr>
									<td>Feminino</td>
									<td align="center">17</td>
									<td align="center">45</td>
								</tr>
								<tr>
									<td>Masculino</td>
									<td align="center">21</td>
									<td align="center">55</td>
								</tr>
								<tr>
									<td><bold>Regurgitação Mitral</bold></td>
									<td> </td>
									<td> </td>
								</tr>
								<tr>
									<td>Ausente</td>
									<td align="center">2</td>
									<td align="center">5,3</td>
								</tr>
								<tr>
									<td>Discreta</td>
									<td align="center">7</td>
									<td align="center">18,4</td>
								</tr>
								<tr>
									<td>Moderada</td>
									<td align="center">12</td>
									<td align="center">31,6</td>
								</tr>
								<tr>
									<td>Acentuada</td>
									<td align="center">17</td>
									<td align="center">44,7</td>
								</tr>
								<tr>
									<td><bold>Regurgitação Tricúspide</bold></td>
									<td> </td>
									<td> </td>
								</tr>
								<tr>
									<td>Ausente</td>
									<td align="center">4</td>
									<td> </td>
								</tr>
								<tr>
									<td>Discreta</td>
									<td align="center">18</td>
									<td> </td>
								</tr>
								<tr>
									<td>Moderada</td>
									<td align="center">8</td>
									<td> </td>
								</tr>
								<tr>
									<td>Acentuada</td>
									<td align="center">8</td>
									<td> </td>
								</tr>
								<tr>
									<td><bold>Etiologia da miocardiopatia</bold></td>
									<td> </td>
									<td> </td>
								</tr>
								<tr>
									<td>Idiopática</td>
									<td align="center">26</td>
									<td> </td>
								</tr>
								<tr>
									<td>Chagásica</td>
									<td align="center">9</td>
									<td> </td>
								</tr>
								<tr>
									<td>Isquêmica</td>
									<td align="center">3</td>
									<td> </td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN1002">
								<p>DDR: dispositivo dielétrico remoto.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>
					<table-wrap id="t2002">
						<label>Tabela 2</label>
						<caption>
							<title>– Variáveis contínuas</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th scope="col">Parâmetros contínuos</th>
									<th scope="col">Mean</th>
									<th scope="col">SD</th>
									<th scope="col">Minimum</th>
									<th scope="col">Maximum</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td>Idade (anos)</td>
									<td align="center">63,2</td>
									<td align="center">12,4</td>
									<td align="center">26</td>
									<td align="center">81</td>
								</tr>
								<tr>
									<td>Pressão arterial sistólica (mmHg)</td>
									<td align="center">112,8</td>
									<td align="center">21,4</td>
									<td align="center">70</td>
									<td align="center">160</td>
								</tr>
								<tr>
									<td>Pressão arterial diastólica (mm Hg)</td>
									<td align="center">72,5</td>
									<td align="center">14,4</td>
									<td align="center">50</td>
									<td align="center">100</td>
								</tr>
								<tr>
									<td>SC (m<sup>2</sup>)</td>
									<td align="center">1,8</td>
									<td align="center">0,2</td>
									<td align="center">1,41</td>
									<td align="center">2,3</td>
								</tr>
								<tr>
									<td>Índice de massa corporal (kg/m<sup>2</sup>)</td>
									<td align="center">29,5</td>
									<td align="center">8,1</td>
									<td align="center">16,5</td>
									<td align="center">55,7</td>
								</tr>
								<tr>
									<td>Diâmetro diastólico do VE (mm)</td>
									<td align="center">66,5</td>
									<td align="center">7,9</td>
									<td align="center">55</td>
									<td align="center">84</td>
								</tr>
								<tr>
									<td>Fração de ejeção VE Simpson (%)</td>
									<td align="center">23,9</td>
									<td align="center">6,7</td>
									<td align="center">15</td>
									<td align="center">40</td>
								</tr>
								<tr>
									<td>Índice de Massa do VE (g/m<sup>2</sup>)</td>
									<td align="center">126,5</td>
									<td align="center">39,4</td>
									<td align="center">69</td>
									<td align="center">246</td>
								</tr>
								<tr>
									<td>Volume indexado do AE (ml/m<sup>2</sup>)</td>
									<td align="center">65,1</td>
									<td align="center">23,4</td>
									<td align="center">31</td>
									<td align="center">158</td>
								</tr>
								<tr>
									<td>Volume indexado do AD (ml/m<sup>2</sup>)</td>
									<td align="center">48,9</td>
									<td align="center">32,9</td>
									<td align="center">14</td>
									<td align="center">172</td>
								</tr>
								<tr>
									<td>Diâmetro basal do VD (mm)</td>
									<td align="center">40,9</td>
									<td align="center">9,3</td>
									<td align="center">20</td>
									<td align="center">61</td>
								</tr>
								<tr>
									<td>Velocidade tecidual do anel lateral VD</td>
									<td align="center">8,2</td>
									<td align="center">2,6</td>
									<td align="center">4</td>
									<td align="center">16</td>
								</tr>
								<tr>
									<td>TAPSE (mmHg)</td>
									<td align="center">14,5</td>
									<td align="center">4,6</td>
									<td align="center">4</td>
									<td align="center">26</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN2002">
								<p>SD: standard deviation; VE: ventrículo esquerdo; VD: ventrículo direito; AE: átrio esquerdo; AD: átrio direito; TAPSE: excursão pelo modo M do anel lateral tricúspide (tricuspid annular plane systolic excursion); SC: superfício corpórea.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>
					<table-wrap id="t3002">
						<label>Tabela 3</label>
						<caption>
							<title>– Comparação entre os grupos DDR&gt;35% e DDR &lt;35%</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left" rowspan="2">Parâmetros</th>
									<th colspan="2">DDR</th>
									<th rowspan="2">p-valor</th>
								</tr>
								<tr>
									<th>&lt; 35%</th>
									<th>≥ 35%</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td><bold>Idade (anos)</bold></td>
									<td align="center">59±14,5</td>
									<td align="center">67±8,3</td>
									<td align="center">0,03</td>
								</tr>
								<tr>
									<td><bold>VTI VSVE</bold></td>
									<td align="center">12,5 ± 4,8</td>
									<td align="center">12,8 ± 4,1</td>
									<td align="center">0,82</td>
								</tr>
								<tr>
									<td><bold>E/ e’ médio</bold></td>
									<td align="center">16,1 ± 7,2</td>
									<td align="center">17,1 ± 7,1</td>
									<td align="center">0,69</td>
								</tr>
								<tr>
									<td><bold>Veia cava inferior (mm)</bold></td>
									<td align="center">17,4 ± 7,3</td>
									<td align="center">17,95 ± 4,6</td>
									<td align="center">0,76</td>
								</tr>
								<tr>
									<td><bold>Colabamento Veia Cava (%)</bold></td>
									<td align="center">42,5 ± 41,5</td>
									<td align="center">33,36 ± 25,4</td>
									<td align="center">0,89</td>
								</tr>
								<tr>
									<td><bold>Pressão estimada do AD (mmHg)</bold></td>
									<td align="center">6,6 ± 5,3</td>
									<td align="center">7,23 ± 4,41</td>
									<td align="center">0,44</td>
								</tr>
								<tr>
									<td><bold>NT pro BNP (pcg/ml)</bold></td>
									<td align="center">4311,4 ± 3289,7</td>
									<td align="center">4267,7 ± 4136,9</td>
									<td align="center">0,97</td>
								</tr>
								<tr>
									<td><bold>Linhas B (unidades)</bold></td>
									<td align="center">7,19 ± 4,43</td>
									<td align="center">9,82 ± 7,43</td>
									<td align="center">0,18</td>
								</tr>
								<tr>
									<td><bold>Tonturas</bold></td>
									<td> </td>
									<td> </td>
									<td align="center">0,97</td>
								</tr>
								<tr>
									<td>Não</td>
									<td align="center">11 (42,31)</td>
									<td align="center">15 (57,69)</td>
									<td> </td>
								</tr>
								<tr>
									<td>Sim</td>
									<td align="center">5 (41,67)</td>
									<td align="center">7 (58,33)</td>
									<td> </td>
								</tr>
								<tr>
									<td><bold>Dispneia paroxística noturna</bold></td>
									<td> </td>
									<td> </td>
									<td align="center">0,19</td>
								</tr>
								<tr>
									<td>Não</td>
									<td align="center">12 (50,00)</td>
									<td align="center">12 (50,00)</td>
									<td> </td>
								</tr>
								<tr>
									<td>Sim</td>
									<td align="center">4 (28,57)</td>
									<td align="center">10 (71,43)</td>
									<td> </td>
								</tr>
								<tr>
									<td><bold>Turgência Jugular</bold></td>
									<td> </td>
									<td> </td>
									<td align="center">0,11</td>
								</tr>
								<tr>
									<td>Não</td>
									<td align="center">4 (26,67)</td>
									<td align="center">11 (73,33)</td>
									<td> </td>
								</tr>
								<tr>
									<td>Sim</td>
									<td align="center">12 (52,17)</td>
									<td align="center">11 (47,83)</td>
									<td> </td>
								</tr>
								<tr>
									<td><bold>EMI</bold></td>
									<td> </td>
									<td> </td>
									<td align="center">0,08</td>
								</tr>
								<tr>
									<td>Não</td>
									<td align="center">11 (50,00)</td>
									<td align="center">9 (45,00)</td>
									<td> </td>
								</tr>
								<tr>
									<td>Sim</td>
									<td align="center">5 (27,78)</td>
									<td align="center">13 (72,22)</td>
									<td> </td>
								</tr>
								<tr>
									<td><bold>Hepatomegalia</bold></td>
									<td> </td>
									<td> </td>
									<td align="center">0,57</td>
								</tr>
								<tr>
									<td>Não</td>
									<td align="center">8 (38,10)</td>
									<td align="center">13 (61,90)</td>
									<td> </td>
								</tr>
								<tr>
									<td>Sim</td>
									<td align="center">8 (47,06)</td>
									<td align="center">9 (52,94)</td>
									<td> </td>
								</tr>
								<tr>
									<td><bold>Troponina</bold></td>
									<td> </td>
									<td> </td>
									<td align="center">0,24</td>
								</tr>
								<tr>
									<td>Alterada (<underline>&gt;</underline> 0,04 ng/ml)</td>
									<td align="center">11 (50,00)</td>
									<td align="center">11 (50,00)</td>
									<td> </td>
								</tr>
								<tr>
									<td>Normal (&lt;0,04 ng/ml)</td>
									<td align="center">5 (31,25)</td>
									<td align="center">11 (68,75)</td>
									<td> </td>
								</tr>
								<tr>
									<td><bold>Creatinina</bold></td>
									<td> </td>
									<td> </td>
									<td align="center">0,66</td>
								</tr>
								<tr>
									<td>Normal (&lt;1,4 mg/dl)</td>
									<td align="center">8 (42,11)</td>
									<td align="center">11 (57,89)</td>
									<td> </td>
								</tr>
								<tr>
									<td>Alteração discreta (1,4-2,0 mg/dl)</td>
									<td align="center">5 (35,71)</td>
									<td align="center">9 (64,29)</td>
									<td> </td>
								</tr>
								<tr>
									<td>Alteração moderada (&gt;2,1 mg/dl)</td>
									<td align="center">3 (60,00)</td>
									<td align="center">2 (40,00)</td>
									<td> </td>
								</tr>
								<tr>
									<td><bold>ICC CF NYHA</bold></td>
									<td> </td>
									<td> </td>
									<td align="center">0,82</td>
								</tr>
								<tr>
									<td>I</td>
									<td align="center">0 (0,00)</td>
									<td align="center">2 (100,00)</td>
									<td> </td>
								</tr>
								<tr>
									<td>II</td>
									<td align="center">8 (47,06)</td>
									<td align="center">9 (52,94)</td>
									<td> </td>
								</tr>
								<tr>
									<td>III</td>
									<td align="center">7 (41,18)</td>
									<td align="center">10 (58,82)</td>
									<td> </td>
								</tr>
								<tr>
									<td>IV</td>
									<td align="center">1 (50,00)</td>
									<td align="center">1 (50,00</td>
									<td> </td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN3002">
								<p>VTIVSVE: integral das velocidades da via de saída do ventrículo esquerdo; E/e’: relação entre a velocidade E de influxo mitral e a média do Doppler tecidual do anel lateral e medial; AD: átrio direito; NT Pro-BNP: dosagem da fração N do peptídeo natriurético atrial tipo B; DDR: dispositivo dielétrico remoto; EMI: edema de membros inferiores; ICC CF NYHA: insuficicência cardíaca classe funciona da New York Heart Association.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>Dados clínicos como superfície corpórea (SC), gênero, presença de tonturas, dispneia paroxística noturna e EMI; NT pró BNP; dados ETT como VAE, VTI da via de saída VE, relação de E/e’ médio, SVD, TAPSE, análise da VCI e contagem de linhas B foram comparados com o ajuste de modelos de Poisson com variância robusta para o resultado de DDR ≥ 35%. Na análise multivariada, as variáveis SC pela razão de prevalência ajustada (RPA): 8,7 (2,7;27,8), p = 0,003; SVD RPA: 1,12 (1,00;1,04), p = 0,03; linhas B RPA: 1,02 (1,00:1,04), p = 0,04 e EMI RPA: 1,56 (1,00;2,57), p = 0,04 se associaram a DDR ≥ 35% (<xref ref-type="table" rid="t4002">Tabela 4</xref>).</p>
				<p>
					<table-wrap id="t4002">
						<label>Tabela 4</label>
						<caption>
							<title>– Análise multivariada com ajuste de variância para DDR&gt;35%</title>
						</caption>
						<table frame="hsides" rules="groups">
							<colgroup>
								<col/>
								<col/>
								<col/>
								<col/>
								<col/>
							</colgroup>
							<thead>
								<tr>
									<th align="left" style="font-weight:normal"> </th>
									<th colspan="2">RP Bruta</th>
									<th colspan="2">RP Ajustada<sup><bold>*</bold></sup></th>
								</tr>
								<tr>
									<th align="left">Variáveis</th>
									<th>RP (IC 95 %)</th>
									<th>p-valor</th>
									<th>RP (IC 95%)</th>
									<th>p-valor</th>
								</tr>
							</thead>
							<tbody>
								<tr>
									<td><bold>Gênero</bold></td>
									<td> </td>
									<td align="center">0,0862</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td>Feminino</td>
									<td align="center">1</td>
									<td align="center">-</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td>Masculino</td>
									<td align="center">1,73 (0,92; 3,25)</td>
									<td align="center">0,09</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Pressão arterial sistólica</bold></td>
									<td align="center">1,01 (1,00; 1,03)</td>
									<td align="center">0,05</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Pressão arterial diastólica</bold></td>
									<td align="center">1,01 (0,99; 1,03)</td>
									<td align="center">0,16</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>SC</bold></td>
									<td align="center">5,41 (2,2; 13,6)</td>
									<td align="center">0,0003</td>
									<td align="center">8,67 (2,71;27,82)</td>
									<td align="center">0,0003</td>
								</tr>
								<tr>
									<td><bold>Indíce de massa corpórea</bold></td>
									<td align="center">1,02 (0,99; 1,06)</td>
									<td align="center">0,25</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Diâmetro diastólico final</bold></td>
									<td align="center">1,02 (0,99; 1,05)</td>
									<td align="center">0,23</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Volume indexado do AE</bold></td>
									<td align="center">1,00 (1,00; 1,01)</td>
									<td align="center">0,34</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>SVD</bold></td>
									<td align="center">1,07 (0,99; 1,20)</td>
									<td align="center">0,06</td>
									<td align="center">1,12 (1,01; 1,24)</td>
									<td align="center">0,0262</td>
								</tr>
								<tr>
									<td><bold>TAPSE</bold></td>
									<td align="center">1,03 (0,97; 1,09)</td>
									<td align="center">0,36</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>VTIVSVE</bold></td>
									<td align="center">1,01 (0,94; 1,07)</td>
									<td align="center">0,82</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>E/ e’ médio</bold></td>
									<td align="center">1,01 (0,97; 1,05)</td>
									<td align="center">0,68</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Veia cava inferior</bold></td>
									<td align="center">1,01 (0,96; 1,06)</td>
									<td align="center">0,78</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Colabamento Veia Cava</bold></td>
									<td align="center">1,00 (0,99; 1,01)</td>
									<td align="center">0,43</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Pressão estimada do AD</bold></td>
									<td align="center">1,01 (0,95; 1,07)</td>
									<td align="center">0,70</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>NT ProBNP</bold></td>
									<td align="center">1.00 (1,00; 1,00)</td>
									<td align="center">0,97</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Linhas B</bold></td>
									<td align="center">1,03 (0,99; 1,06)</td>
									<td align="center">0,09</td>
									<td align="center">1,02 (1,00; 1,04)</td>
									<td align="center">0,0403</td>
								</tr>
								<tr>
									<td><bold>Tonturas Queda PA</bold></td>
									<td> </td>
									<td align="center">0,97</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td>Não</td>
									<td align="center">1</td>
									<td align="center">-</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td>Sim</td>
									<td align="center">1,01 (0,57; 1,81)</td>
									<td align="center">0,97</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Dispneia paroxística noturna</bold></td>
									<td> </td>
									<td align="center">0,17</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td>Não</td>
									<td align="center">1</td>
									<td align="center">-</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td>Sim</td>
									<td align="center">1,43 (0,85; 2,40)</td>
									<td align="center">0,18</td>
									<td align="center">-</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td><bold>Edema de MMII</bold></td>
									<td> </td>
									<td align="center">0,09</td>
									<td> </td>
									<td align="center">0,0479</td>
								</tr>
								<tr>
									<td>Não</td>
									<td align="center">1</td>
									<td align="center">-</td>
									<td align="center">1</td>
									<td align="center">-</td>
								</tr>
								<tr>
									<td>Sim</td>
									<td align="center">1,60 (0,91; 2,82)</td>
									<td align="center">0,09</td>
									<td align="center">1,56 (1,00; 2,57)</td>
									<td align="center">0,0479</td>
								</tr>
							</tbody>
						</table>
						<table-wrap-foot>
							<fn id="TFN4002">
								<p>AE: átrio esquerdo; SVD: velocidade sistólica do doppler tecidual do anel lateral tricúspide; TAPSE: excursão pelo modo M do anel lateral tricúspide (tricuspid annular plane systolic excursion); VTIVSVE: integral das velocidades da via de saída do ventrículo esquerdo; E/e’: relação entre a velocidade E de influxo mitral e a média do Doppler tecidual do anel lateral e medial; AD: átrio direito; NT Pro-BNP: dosagem da fração N do peptídeo natriurético atrial tipo B; SC: superfície corpórea; RP: razão de prevalência; PA: pressão arterial; MMII: membros inferiores.</p>
							</fn>
						</table-wrap-foot>
					</table-wrap>
				</p>
				<p>NT-ProBNP foi semelhante e elevado em ambos os grupos e sem correlação com DDR (4311 ± 3289 mg/dl para DDR &lt;35% e 4267 ± 4136 mg/dl para a DDR ≥ 35%, p = 0,97) (<xref ref-type="table" rid="t4002">Tabela 4</xref>).</p>
				<p>A variabilidade entre observadores para contagem de linhas B se realizou em imagens armazenadas de 20 pacientes e o coeficiente de correlação foi de 97%.</p>
			</sec>
			<sec sec-type="discussion">
				<title>Discussão</title>
				<p>O principal achado deste estudo piloto em pacientes com ICFER de difícil controle terapêutico volêmico foi a correlação significativa que as linhas B do ULSP apresentam com um dispositivo de alta acurácia para detecção de congestão pulmonar dispositívo dielétrico remoto (DDR). Desta forma, há possibilidade da utilização do ULSP no controle de congestão pulmonar ambulatorial, minimizando custos de internações frequentes e otimizando o uso de diuréticos.</p>
				<p>O DDR apresenta uma excelente correlação com a tomografia de tórax para detecção de congestão pulmonar com uso de um software de análise de densidade pulmonar em pacientes com ICFER descompensada e voluntários normais,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> bem como com a pressão de capilar pulmonar por medida invasiva.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> No entanto, não há estudos comparando a quantidade de linhas B do USLP ambulatorial em pacientes com ICFER e o DDR como padrão ouro.</p>
				<p>O uso do ULSP para avaliação de congestão pulmonar está bem estabelecido. No estudo multicêntrico conduzido pela SIMEU (<italic>Study and Research Centre of the Italian Society of Emergency Medicine</italic>), observou-se que a avaliação clínica associada à detecção de linhas B no ULSP demonstrava uma acurácia de 97% na detecção de congestão pulmonar, número que superou o próprio NT-ProBNP, o qual apresentou somente 62% de acurácia.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Estes achados são concordantes com nosso estudo, no qual as linhas B se correlacionaram com DDR ≥ 35%, e o NT-ProBNP, apesar de elevado em ambos os grupos, não mostrou correlação com o DDR.</p>
				<p>O aumento de linhas B observado no ULSP, além de auxiliar o diagnóstico da causa de dispneia na emergência,<sup><xref ref-type="bibr" rid="B22">22</xref></sup> está associado à maior número de internações<sup><xref ref-type="bibr" rid="B23">23</xref></sup> e pior prognóstico em pacientes pós infarto do miocárdio.<sup><xref ref-type="bibr" rid="B24">24</xref></sup> Miglioranza et al.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> demostraram que o achado de 15 linhas B no ULSP indicava uma possibilidade de descompensação iminente de pacientes em acompanhamento ambulatorial, mas não comparou os achados de congestão pelo ULSP com algum padrão ouro. Nosso estudo conseguiu determinar em comparação a um padrão ouro (DDR) que as linhas B em pacientes ambulatoriais com ICFER se correlacionam com maior congestão pulmonar em pacientes com difícil controle volêmico.</p>
				<p>Com relação a parâmetros de congestão sistêmica, encontrou-se correlação com DDR<underline>&gt;</underline>35% somente na avaliação da função longitudinal pelo doppler tecidual do ventrículo direito (SVD) e o achado no exame físico de EMI. Era esperado que o DDR não apresentasse correlação com parâmetros de congestão sistêmica pelo fato de medir quantidade de líquido extravascular pulmonar. No entanto, possivelmente pacientes com maior congestão pulmonar e disfunção do VD podem apresentar maior congestão sistêmica e por consequência, EMI.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B2">2</xref></sup></p>
				<p>A SC indicou boa correlação com o DDR, pois o cálculo utilizado pelo dispositivo depende do peso e altura do paciente.<sup><xref ref-type="bibr" rid="B11">11</xref></sup></p>
				<sec>
					<title>Potenciais limitações e forças do estudo</title>
					<p>A principal limitação do estudo é o número pequeno de pacientes, todos incluídos em um centro único. Outra possível limitação foi a não realização de medidas invasivas que pudessem detectar diretamente pressões de enchimento para comparação com a quantidade de linhas B e o DDR.</p>
					<p>Tendo em vista que, mesmo com o número reduzido de indivíduos incluídos no estudo, a correlação de linhas B com DDR <underline>&gt;</underline>35% foi significativa, este resultado é a principal força do estudo, pela alta sensibilidade da detecção de linhas B pelo ULSP em pacientes com difícil controle volêmico.</p>
				</sec>
			</sec>
			<sec sec-type="conclusions">
				<title>Conclusão</title>
				<p>Neste estudo piloto, o ULSP apresentou boa correlação com a congestão pulmonar medida por um dispositivo de alta acurácia (DDR) e pode ser uma ferramenta muito útil no controle ambulatorial de pacientes com ICFER, minimizando internações e melhorando o controle volêmico nestes pacientes.</p>
				<p>Dos parâmetros de congestão sistêmica, somente o SVD (medida de função longitudinal do VD) foi significativo, indicando que pacientes com maior disfunção do VD apresentam concomitância entre congestão pulmonar e congestão sistêmica.</p>
			</sec>
		</body>
		<back>
			<ack>
				<title>Agradecimentos</title>
				<p>Os autores agradecem o trabalho primoroso do professor Eduardo Freitas da Silva na correção e orientação da análise estatística.</p>
			</ack>
			<fn-group>
				<fn fn-type="other">
					<p>Vinculação Acadêmica</p>
					<p>Não há vinculação deste estudo a programas de pós-graduação.</p>
				</fn>
				<fn fn-type="other">
					<p>Aprovação Ética e Consentimento Informado</p>
					<p>Este estudo foi aprovado pelo Comitê de Ética do Instituto Dante Pazzanese sob o número de protocolo 532248210.0000.5462. Todos os procedimentos envolvidos nesse estudo estão de acordo com a Declaração de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes incluídos no estudo.</p>
				</fn>
			</fn-group>
			<fn-group>
				<fn fn-type="supported-by">
					<p>Fontes de Financiamento: O presente estudo não teve fontes de financiamento externas.</p>
				</fn>
			</fn-group>
		</back>
	</sub-article>
</article>